Alkyl esters of alpha-cyano-beta-furylidene acetic acid as insect repellents



Patented Feb. 10, 1948 ESTERS OF a -CYANO-fl-FURYLIDENE ACE'IIC ACID A8INSECT BEPEILENTS MI! a. 1m], New Brunswick, N. 3., minimto Merck a 00..Inc., Railway,

! New Jersey N. a corporation No Drawing. Application 0mm 21, 1943.Serial a. 507,891

3 Claiml. (CL 167-30) .This invention relates to insect repellents, andits primary object is to provide substances 0! improved eiilciency inrepelling various insect pests, particularly mosquitoes.

In'oi'der to be satisfactory as an insect re pellent, a substance, orcomposition of matter,

selected for this purpose must possess a high degree of repellency whichwill be eflective for prolonged periods of time. In addition, suchagents must be non-toxic and otherwise harmless to the individualstreated. Many substances have been suggested for use as insectrepellents,

heretofore, but for one reason or another, have not been found entirelysatisfactory. Thereis a pressing need in the art for an insect repellentwhich will be truly efiective, and which will aid in obviating theincidence of untoward physiological effects which may be brought aboutby the transmittal of diseases through insect bites.

I have now discovered that lower alkyl esters of c-cyano-fi-furylideneacetic acid, such as the ethyl, methyl esters, etc., are extremelyeffective insect repellents, when adapted according to my invention, andmeet the stringent requirements or present day needs for suchsubstances.

Insect repellents are most desirably applied to the individual to betreated in a carrier or base. Ihave discovered that when the alkylesters of e-cyano-p-furylidene acetic acid are incorporated with certaincommonly known carriers or vehicles which have been suggested.heretofore,

for use with insect repellents, the activity of the esters is eitherlost altogether or seriously impaired. Therefore, it is a further objectof our invention to provide especially selected carriers or solvents forsuch alkyl esters of a-cyano-B- Iurylidene acetic acid so that fullbenefit of the repellency properties of the esters. is obtained.

-The selection of a solvent or carrier for such purposes is an importantfeature of my invention since the solvent or carrier markedly aiiectsthe eillcacy of the a-cyano-p-furylidene acetic acid esters.

Solvents which have been shown by my tests to be admirably suited for myintended purposes are lower alkyl esters or polybasic acids, such asdimethyl phthalate, dimethyl adipate, and nwbutyl citrate. In someinstances the solvents may be used in combination. Thus, I have foundthat a mixture of dimethyl adipate and n-butyl citrate is highlysuitable for use as a vehicle for lower alkyl esters ofu-cyano-p-furylidene acetic acid.

I have i'ound that compositions comprising the acid, and the lower alkylesters oi. polybasic acids, as described, may employed with ease anded!- ciency in accordance with the methods described hereinafter. Therepellent action of the Iurylidene acetic acid esters is unimpaired whensolutions thereof in the solvents of the type described herein areutilized; in fact, the solvents have, themselves, to a certain degree,an insect repelling action, and their use in conjunction with the alkylesters of a-cyano-fl-iuryiidene acetic acid, in accordance with myinvention, results in a synergistic effect so that a greater thanadditive effect as regards insect repellency is generally obtained inthe resulting composition.

The lower alkyl esters oi -cyano-p-lurylidene acetic acid are prepared,according to the process disclosed in Berichte 27, 2625 and Beilstein17, 275 and illustrated by the reaction Ire-0H ON H t -crhc-coon where Ris lower alkyl.

The compositions of my invention are prepared by dissolving convenientamounts of the desired previously suggested for use as repellents, suchas the essential oils including citronella, these materials are almostodorless, or of an odor which is pleasing to human beings. Preparationscomprising these materials do not exhibit an irritating effect upon theskin, and do not aiiect clothing adversely.

The repellent action not the compositions according to my invention hasbeen determined by exhaustive tests. Themethod of performing these testsis as follows:

The test insect is the adult female mosquito Ades aegypti, which is fourdays old from the time of emergence. From emergence, to the period oftesting, the mosquitoes have been fed on moist raisins, and have neverreceived a blood meal.

One hundred female mosquitoes are placed in lower alkyl esters ora-cyano-p-furylidene acetic II a cubical cage. 24 inches on edge, whichis closed on the bottom and front, and enclosed on the remaining threesides and top by marquisette or a similar material.

The operator who is to make the test coats one arm from the wrist to theelbow with 0.6 cc. of the repellent mixture per 60 square inches, or0.01 cc. per square inch. The material is spread over the arm by meansof a pipette and then spread out by means of a glass rod whichpreviously has been dipped into the mixture and allowed to drain.

When it is desired to take a reading, the untreated arm is inserted inthe cage and waved about so as to stimulate the'mosquitoes, but they arenot permitted to feed on it. As soon as the majority of the mosquitoesare activated, the arm is .held still for one minute, and the number ofbites determined which gives the bite rate at the start. The treated armis then inserted into the cage, with the entire treated area exposed andkept still for five minutes. The first reading is made one hour afterapply the material to the arm. Subsequent readings are taken at /2 hourintervals until the breakpoint is obtained. The breakpoint is taken asthe first breaking of the skin by the mosquito, but which is confirmedby penetrations on two successive half-hour interval tests. The timerequired for the breakpoint, and confirmation thereof, is taken as theperiod of "complete protection against insect attack. The use of thepreparations of my invention also furnishes a period of partial prtection against insect attack, which may be defined as that period oftime subsequent to the complete protection" period, during which theoperator does not get more than five brief penetrations by themosquitoes during a five-minute test period. A brief penetration may bedescribed as that penetration experienced when the mosquito attempts tosink his proboscis into the skin but is repelled after having penetratedonly through the outer layer of skin. A deep penetration occurs when themosquito. sinks his proboscis into the skin to such a depth that hisheadbecomes lower than the remainder of his Table I illustrates theresults obtained by testing a-cyano-p-furylidene acetic acid ethyl esterin a number of especially selected vehicles (Indalone is essentially thecompound cam-C11- methyl -carbobutoxy-,p-dihydro-gamma-pyrone.) I

When a composition comprising 10% of the ethyl ester ofa-cyano-fi-furylidene acetic acid in a mixture of dimethyl adipate andn-butyl citrate (1:1) was tested under actual trial con- 5 'ditions forrepellency against the Adirondack black fiy (Prosimulium hirtipes) andthe whitestocking black fly (Simulium venustum) it was found to afford5.5 hours of complete protection on one trial and 3.5 hours of completeprotection on another trial under more severe conditions. The samecomposition was tested under actual trial conditions against punkies(Culicoides sp.) and it afforded 6 hours of complete protection.

The effectiveness of my insect repellent compositions has been comparedwith that of other Table II Complete I Material Tested Protection,

Hours But i carbitol acetate 3 In alone" 3.5 E verready Insect RepellentFormula 612 b. 5 Dimethyl phthalate 7. 5

(The active ingredient of "Everready Insect Repellent Formula 612 is2-ethylhexanediol-L3.)

It will be apparent from the foregoing experimental results that thepreparations according to my invention possess unusual properties, andthat they are peculiarly eflicacious when used as insect repellents.

Modifications may be made in carrying out the present invention withoutdeparting from the spirit and scope thereof, and I am to be limited onlyby the appended claims.

I claim: 1. An insect repellent comprising a solution ofa-cyano-p-furylidene-aotic acid ethyl ester in a (ii-lower alkylphthalate.

-2. An insect repellent comprising a solution ofa-cyano-p-furylidene-acetic acid ethyl esther in dimethyl phthalate.

3. An insect repellent comprising a solution of about 17.5% ofa-cyano-p-furylidene-acetic acid ethyl ester in dimethyl phthalate.

REFERENCES orrnn The following references are of record in the file ofthis patent:

Industrial Solvents by Mellan 1939 ed., page 423. (Copyin Div. 50.)

Beilstein V. 18 (1934) ad, page Div. 6.)

338. (Cops in

